Abstract
Endometrial cancer (EC) is the sixth most common cancer in women worldwide and its mortality is directly associated with the presence of poor prognostic factors driving tumor recurrence. Stratification systems are based on few molecular, and mostly clinical and pathological parameters, but these systems remain inaccurate. Therefore, identifying prognostic EC biomarkers is crucial for improving risk assessment pre- and postoperatively and to guide treatment decisions. This systematic review gathers all protein biomarkers associated with clinical prognostic factors of EC, recurrence and survival. Relevant studies were identified by searching the PubMed database from 1991 to February 2020. A total number of 398 studies matched our criteria, which compiled 255 proteins associated with the prognosis of EC. MUC16, ESR1, PGR, TP53, WFDC2, MKI67, ERBB2, L1CAM, CDH1, PTEN and MMR proteins are the most validated biomarkers. On the basis of our meta-analysis ESR1, TP53 and WFDC2 showed potential usefulness for predicting overall survival in EC. Limitations of the published studies in terms of appropriate study design, lack of high-throughput measurements, and statistical deficiencies are highlighted, and new approaches and perspectives for the identification and validation of clinically valuable EC prognostic biomarkers are discussed.
Highlights
IntroductionEndometrial cancer (EC) is the sixth most common cancer in women worldwide and the most common tumor of the female genital tract
From the 398 reviewed studies, a total of 255 protein biomarkers were identified as potential prognostic biomarkers, defined as proteins that are associated with one or more of the known clinical prognostic factors in Endometrial cancer (EC), recurrence or survival
From the 255 protein biomarkers compiled in this review, only 21% were validated by using either an independent technique, an independent cohort, or in an independent study
Summary
Endometrial cancer (EC) is the sixth most common cancer in women worldwide and the most common tumor of the female genital tract. A total number of 382,069 new estimated cases and 89,929 estimated deaths were reported for 2018 [1]. EC incidences have been increasing in the last years as a consequence of the populations increasing life expectancy and a higher overall prevalence of obesity and metabolic syndromes. Unlike many other malignancies, EC mortality has been increasing [2]. The number of new cases and deaths is expected to increase by 20.3% and 17.4% by 2025, respectively [1]. Mortality of EC patients is directly associated to the presence of poor prognostic factors, which drive tumor recurrence
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